Linked Life Data

10839475

Source:http://linkedlifedata.com/resource/pubmed/id/10839475

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-8-17
pubmed:abstractText
Diethylhexylphthalate (DEHP) is a phthalate plasticizer that belongs to the peroxisome proliferator (PP) class of rodent nongenotoxic hepatocarcinogens. Previously, we have shown that MEHP (a principal metabolite of DEHP and the proximal PP) induced DNA synthesis and suppressed apoptosis in rat but not in human hepatocytes in vitro. Here, we present further studies of species differences in response to DEHP. In rats, 4 days of exposure to DEHP (950 mg/kg per day by gavage) induced peroxisomal beta-oxidation, DNA synthesis and suppressed apoptosis. In contrast, there was no response of guinea pig liver to DEHP. In rat hepatocytes in vitro, MEHP (250, 500 and 750 microM) induced peroxisomal beta-oxidation, DNA synthesis and suppressed apoptosis. In contrast to the pleiotropic response noted in rat hepatocytes, there was no response of human hepatocytes to 250, 500 or 750 microM MEHP. PPs activate the peroxisome proliferator activated receptor alpha (PPARalpha) that binds to DNA at peroxisome proliferator response elements (PPREs) within the promoters of PP-responsive genes such as rat acyl CoA oxidase (ACO). However, the human ACO gene promoter differs at three bases within the PPRE from the rat ACO promoter and appears refractory to PPs. To address species differences in response to DEHP at the molecular level, we used promoter-reporter gene assays to compare the ability of MEHP to induce gene expression from the rat or the human ACO promoter. MEHP gave a concentration-dependent increase in reporter gene expression from the rat ACO gene promoter with either mouse or human PPARalpha. In contrast, the human ACO promoter was unable to drive MEHP-induced gene transcription irrespective of the species origin of PPARalpha. These data provide further weight of evidence at the cellular and molecular levels for a lack of risk to human health from the phthalate DEHP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0340-5761
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
85-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10839475-3T3 Cells, pubmed-meshheading:10839475-Animals, pubmed-meshheading:10839475-Apoptosis, pubmed-meshheading:10839475-DNA, pubmed-meshheading:10839475-DNA Replication, pubmed-meshheading:10839475-Diethylhexyl Phthalate, pubmed-meshheading:10839475-Epidermal Growth Factor, pubmed-meshheading:10839475-Gene Expression, pubmed-meshheading:10839475-Genes, Reporter, pubmed-meshheading:10839475-Guinea Pigs, pubmed-meshheading:10839475-Humans, pubmed-meshheading:10839475-In Situ Nick-End Labeling, pubmed-meshheading:10839475-Liver, pubmed-meshheading:10839475-Male, pubmed-meshheading:10839475-Mice, pubmed-meshheading:10839475-Microbodies, pubmed-meshheading:10839475-Nafenopin, pubmed-meshheading:10839475-Oxidation-Reduction, pubmed-meshheading:10839475-Peroxisome Proliferators, pubmed-meshheading:10839475-Rats, pubmed-meshheading:10839475-Rats, Inbred F344, pubmed-meshheading:10839475-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:10839475-Species Specificity, pubmed-meshheading:10839475-Transcription Factors, pubmed-meshheading:10839475-Transforming Growth Factor beta, pubmed-meshheading:10839475-beta-Galactosidase
pubmed:year
2000
pubmed:articleTitle
Species differences in response to diethylhexylphthalate: suppression of apoptosis, induction of DNA synthesis and peroxisome proliferator activated receptor alpha-mediated gene expression.
pubmed:affiliation
Cancer Biology Group, Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom.
pubmed:publicationType
Journal Article, Comparative Study